Osteoarthritis (OA) represents the most common joint disease, affecting approximately 40 million Americans. OA is a leading cause of severe activity limitations and disability. Therapies that definitively alter the course of the disease are not available. Pharmacologic management of OA is limited to pain control. Nonsteroidal anti-inflammatory drugs are widely used but are associated with significant adverse reactions. Oral glucosamine and chondroitin sulfate are consumed by a large number of patients. Although some studies suggest that this reduces the rate of joint space narrowing, this conclusion is not uniformly accepted. Viscosupplementation with hyaluronan acid or its derivatives has been approved as a therapy for patients with knee OA and clinical experience demonstrated excellent patient compliance. This establishes the need for second-generation products with improved efficacy towards symptom control and disease modification. The key advantage of intraarticular therapy is in the delivery of high local drug concentrations and a reduced risk for systemic adverse reactions. The following proposal is based on prior research to identify novel effective and safe approaches to this form of OA therapy. We observed chondroprotective activities of the glucosamine derivative,N-acetylglucosamine (GIcNAc). Intraarticular injections of aqueous solutions of GIcNAc in 6 rabbits with experimental OA demonstrated greater efficacy than hyaluronan in reducing not only joint inflammation but also cartilage degradation. Adverse reactions were not observed. Based on these findings we propose the hypothesis that intra articular administration of GIcNAc represents a novel, effective and safe approach to chondroprotection. The following aims will address this hypothesis: 1. Prepare formulations of GIcNAc and retention time in rodent joints. 2. Assess therapeutic efficacy of GIcNAc formulations in rabbits with experimentally induced OA. These studies have the potential to provide the basis for a safe and effective chondroprotective therapy for OA.